The mouse major histocompatibility complex (H-2) controls many traits that are important to research on transplantation, viral oncogenesis, disease resistance, and fundamental genetic and immunologic mechanisms. The broad, long-range objective of this proposed research is the elucidation of the number, organization, function and regulation of the multiple genes of the H-2 complex, especially the genes of the I region that control specifc immune responses, lymphoid cell interactions, the mixed leukocyte reaction (MLR), and the Ia lymphocyte antigens. Three general approaches are being pursued: 1) Genetic Organization--large scale screening for recombination and mutation within the complex are being undertaken. H-2 variants detected are extensively characterized for H-2 associated traits, in order to separate, identify, and map the controlling genes. Particular attention is given to analyses of I region traits; 2) Genetic Function-- to elucidate the functions of certain specific genes, more intensive studies are being done on selected traits. The relationship of Ia antigens to many other I region traits and functions is being probed by analyses of capacity of anti-Ia sera to inhibit specific lymphocyte functions. The Ss-Slp proteins are being analyzed for their hormonal regulation and relationship to the complement system. 3) Molecular Characterization--Biochemical analyses of the Ss and Slp proteins are being done to determine their molecular relationships and genetic control. The H-2G antigens are being further analyzed biochemically and serologically. A search for additional serological variant systems in the H-2 complex will also be made.